Triosephosphate Isomerase Inhibition by Resveratrol: A New Mechanism of Anti-Glycolysis in Breast Cancer

IF 1.5 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Biology Pub Date : 2024-09-11 DOI:10.1134/s0026893324700663

G. Tuna, O. Akgün, F. Arı

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Abstract

Breast cancer cells undergo a process of reprogramming their metabolism for rapid growth and proliferation. One of the most common metabolic changes is aerobic glycolysis (Warburg effect), which leads to increased lactate generation and glucose uptake capacity. Triosephosphate isomerase (TPI) is a key enzyme in glycolysis. The effect of Resveratrol (RES), a natural plant compound with known anti-cancer properties, on the TPI enzyme is unknown. The purpose of this study is to examine how RES relates to TPI in breast cancer. TPI levels were examined by ELISA and western-blotting methods in MCF-7 and MDA-MB-231 cells. The changes in lactate dehydrogenase (LDH) activity, methylglyoxal (MGO) formation, nitric oxide synthase (eNOS and iNOS) levels, and MAPK signaling pathway were investigated by colorimetric assays and western-blotting. It was shown for the first time that RES induced a significant decrease in TPI in a dose-dependent manner, with a concomitant increase in levels of MGO, a toxic intermediate. Furthermore, RES treatment decreased LDH activity, and the expression of MAPK, ERK1/2, and JNK, while increasing the expression of eNOS and iNOS levels. The results sign a potential cytotoxic effect of RES due to increased MGO levels resulting from TPI inhibition. The effect of RES on TPI function and glycolysis may be related to NOS induction and the MAPK pathway. These findings are the first data showing the effect of RES treatment on TPI, suggesting that TPI may be a target for energy metabolism in breast cancer.

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白藜芦醇对磷酸三糖异构酶的抑制：乳腺癌抗糖酵解的新机制

摘要乳腺癌细胞为了快速生长和增殖，会经历一个新陈代谢重编程的过程。最常见的新陈代谢变化之一是有氧糖酵解（沃伯格效应），它会导致乳酸生成和葡萄糖摄取能力增加。三磷酸异构酶（TPI）是糖酵解过程中的一种关键酶。白藜芦醇（RES）是一种具有已知抗癌特性的天然植物化合物，其对 TPI 酶的影响尚不清楚。本研究旨在探讨 RES 与乳腺癌中 TPI 的关系。通过酶联免疫吸附法和西方印迹法检测了 MCF-7 和 MDA-MB-231 细胞中的 TPI 水平。比色法和西方印迹法研究了乳酸脱氢酶（LDH）活性、甲基乙二醛（MGO）形成、一氧化氮合酶（eNOS 和 iNOS）水平和 MAPK 信号通路的变化。研究首次表明，RES 可诱导 TPI 以剂量依赖的方式显著下降，同时毒性中间体 MGO 的水平升高。此外，RES 还能降低 LDH 活性以及 MAPK、ERK1/2 和 JNK 的表达，同时提高 eNOS 和 iNOS 的表达水平。这些结果表明，RES 可能具有细胞毒性作用，因为抑制 TPI 会导致 MGO 水平升高。RES 对 TPI 功能和糖酵解的影响可能与 NOS 诱导和 MAPK 通路有关。这些发现是首次有数据显示RES治疗对TPI的影响，表明TPI可能是乳腺癌能量代谢的靶点。

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来源期刊

Molecular Biology 生物-生化与分子生物学

CiteScore

1.30

自引率

8.30%

发文量

审稿时长

3 months

期刊介绍： Molecular Biology is an international peer reviewed journal that covers a wide scope of problems in molecular, cell and computational biology including genomics, proteomics, bioinformatics, molecular virology and immunology, molecular development biology, molecular evolution and related areals. Molecular Biology publishes reviews, experimental and theoretical works. Every year, the journal publishes special issues devoted to most rapidly developing branches of physical-chemical biology and to the most outstanding scientists.